National Cancer Institute

at the National Institutes of Health

General Information About Transitional Cell Cancer of the Renal Pelvis and Ureter

Incidence and Mortality

Transitional cell carcinoma of the renal pelvis, accounting for only 7% of all
kidney tumors, and transitional cell cancer of the ureter, accounting for only
1 of every 25 upper tract tumors, are curable in more than 90% of patients if
they are superficial and confined to the renal pelvis or ureter. Patients with
deeply invasive tumors that are still confined to the renal pelvis or ureter
have a 10% to 15% likelihood of cure. Patients with tumors with penetration
through the urothelial wall or with distant metastases usually cannot be cured
with currently available forms of treatment.

Prognosis

The major prognostic factor at
the time of diagnosis of upper tract transitional cell cancer is the depth of
infiltration into or through the uroepithelial wall.

Most superficial tumors are likely to be well differentiated, while infiltrative tumors
are likely to be poorly differentiated. The incidence of
synchronous or metachronous contralateral upper tract cancers ranges from 2% to
4%; the incidence of subsequent bladder cancer after prior upper tract
transitional cell cancer ranges from 30% to 50%.[1] When involvement of the
upper tract is diffuse (involving both the renal pelvis and ureter), the
likelihood of subsequent development of bladder cancer increases to 75%. DNA
ploidy has not added significant prognostic information beyond that provided by
stage and grade.[2]

Diagnostics

Even if
ureteroscopy and pyeloscopy are successfully implemented, accurate assessment
of depth of invasion is difficult.

Treatment Management and Survivorship

Total excision of the ureter
with a bladder cuff, renal pelvis, and kidney is recommended in an attempt to
provide the greatest likelihood of cure.

Cellular Classification of Transitional Cell Cancer of the Renal Pelvis and Ureter

The majority of upper tract uroepithelial tumors are of transitional cell
histology. Squamous cell cancer of the urinary tract constitutes less than 15%
of the tumors of the renal pelvis and a smaller percentage of ureteral tumors
and is often associated with chronic calculus disease and infection.

Grade of transitional cell cancer of the upper tract has generally been found
to correlate with stage. Superficial tumors are generally grade I or II,
whereas the majority of infiltrative tumors are grades III and IV. Prognosis
is worse for patients with high-grade (grades III and IV) tumors than for those
with low-grade (grades I and II) tumors.

Stage Information for Transitional Cell Cancer of the Renal Pelvis and Ureter

Though comparable in many respects to staging systems described for bladder
cancer, unique structural aspects of the renal pelvis and ureter have led to
several differences in the classification schema of tumors that involve the
upper tracts. Clinical staging is based on a combination of radiographic
procedures (e.g., intravenous pyelogram and computed tomographic scans) and,
more recently, ureteroscopy and biopsy.

The advent of rigid and flexible ureteroscopic techniques has permitted
endoscopic access to the ureter and renal pelvis. This may permit greater
accuracy in preoperative definition of the stage and grade of an upper tract
neoplasm. In addition, fulguration and endourological access permit resection
or laser coagulation of highly selected low-stage, low-grade lesions of the
ureters.[1] However, this approach is still under clinical evaluation since
there is the possibility of inaccurate assessment of the stage and extent of
disease, and the adequacy and risks of such treatment have not yet been
defined.[2-5]

Because of the inaccessibility of ureteral and pelvic anatomy, accurate staging
requires pathologic analysis of the surgically excised specimen.

Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification to define carcinoma of the renal pelvis and ureter.[6]

Group 2: Grade I–III carcinomas without demonstrable subepithelial invasion or
focal microscopic invasion or papillary carcinomas with carcinoma in situ and/or carcinoma in situ elsewhere in the urothelium.

Group 3: High-grade tumors that have infiltrated the renal pelvic wall or renal
parenchyma or both but are still confined to the kidney. Infiltration of
muscle in the upper tract may not be associated with as much potential for
distant dissemination as appears to be the case for bladder cancer.

Regional

Group 4: Extension of tumors beyond the renal pelvis or parenchyma and invasion
of peripelvic and perirenal fat, lymph nodes, hilar vessels, and adjacent
tissues.

Metastatic

Spread of the tumor to distant tissues.

Each of these classifications has been subclassified into categories of
unicentricity or multicentricity. The latter category indicates a more pervasive tumor
diathesis and generally a less favorable prognosis.

Although the classifications listed above have prognostic significance, they
can only be determined at the time of nephroureterectomy, which is the
treatment of choice for patients with this disease. Because of the high
incidence of tumor recurrence within the intramural ureter among patients who
have had incomplete excision of this area, nephroureterectomy should include
the entire ureter and a margin of periureteral orifice mucosa (i.e., bladder cuff).

A TNM system for staging has been established and has demonstrated accurate
predictions of survival. The TNM staging system may be a better predictor of
prognosis than tumor grade, though both are strongly predictive of survival.
Median survival for patients with tumors confined to the subepithelial
connective tissue was 91.1 months compared to 12.9 months for patients with
tumors invading the muscularis and beyond in one report. Flow cytometry analysis
identifies low-stage, low-grade tumors at high risk of recurrence by virtue of
their aneuploid histograms.[7,8]

Treatment Option Overview

The rarity of synchronous bilateral renal pelvic neoplasia, the low incidence
of asynchronous development of contralateral upper tract tumors, and the
increased risk of tumor recurrence in the ipsilateral ureter distal to the
original pelvic tumor are the rationale for total nephroureterectomy with
bladder cuff for most patients with renal pelvic transitional cell cancers and
ureteral cancers.

Contemplation of anything less than total excision must take into account the
potential risk for tumor recurrence anywhere in the upper tract unit. In other
than unifocal, low-grade, low-stage renal pelvic tumors, the probable extensive
involvement of both contiguous and noncontiguous sites would appear to make
segmental excision an unnecessary option with a potentially serious risk.
However, an operative possibility includes segmental excision of a particular
lesion. If the extent of a tumor can be determined by intraoperative
assessment, and frozen section histologic diagnosis confirms low-grade,
unifocal tumor of limited size, then segmental excision is possible. However,
this approach should be reserved for highly selected patients. This includes
those patients who have a solitary kidney or those with decreased renal
function and who require maximal preservation of renal tissue. The likelihood
of tumor recurrence in this setting, and of extension of disease outside the
renal pelvis once the pelvis has been violated, is a serious risk that must be
heavily weighed in offering a patient this therapeutic option.

Ureteral transitional cell cancer may more readily offer the possibility of
segmental excision if the absence of proximal disease can be documented. In
this setting, attention is focused on the ease of reconstruction of the ureter
and restoration of ureterovesical continuity. This is most feasible if the
cancer is in the distal ureter. If partial ureterectomy is possible and
proximal disease has been excluded, then segmental excision and ureteral
reimplantation can be performed.

Systematic regional lymph node dissection in conjunction with
nephroureterectomy or segmental excision has not been found to enhance the
effectiveness of surgery if tumors are of high grade or high stage, since in
these instances the overall results are so poor. Correspondingly, lymph node
involvement is uncommon in low-stage disease, and lymphadenectomy is therefore
unlikely to remove additional tumor. Thus, lymph node dissection at the time
of nephrectomy may offer prognostic information, but little, if any,
therapeutic benefit.

Localized Transitional Cell Cancer of the Renal Pelvis and Ureter

Standard treatment options:

Nephroureterectomy with cuff of bladder.

Segmental resection of ureter, only if the tumor is superficial and located
in the distal third of the ureter.

Treatment options under clinical evaluation:

The development of new instrumentation for endourological treatment of upper
tract transitional cell cancer has provided new options for regional management
of these cancers. Introduction of electrofulguration and resection instruments
or laser probes either transureterally or percutaneously may permit destruction
of a primary cancer. Introduction of cytotoxic agents has also been employed.
Although a biopsy can be taken for staging purposes, the accuracy of this
remains to be determined. The efficacy of treatment by these maneuvers has not
been established.

Electroresection and fulguration or laser fulguration, if the tumor is
superficial.

Any parenchymal sparing procedure (segmental resection; ureteroscopic or
percutaneous resection/fulguration/laser destruction) if the renal unit is
solitary or renal function is depressed.

Intrapelvic or intraureteral cytotoxic/immunotherapy. The dramatic
successes that have been reported with intravesical cytotoxic (thiotepa,
mitomycin, doxorubicin) or immunologic/inflammatory (BCG, interferon) therapy
for superficial transitional cell cancers in the bladder have led to the
occasional use of these agents in the treatment of upper tract cancers.
Long-term follow-up of the results of such treatments has generally not been
reported, and the efficacy of this approach cannot be assessed, largely because
experience has been limited to those patients whose compromised clinical status
(solitary kidney, renal failure, medical risks for surgery) may have influenced
clinical outcome. The use of this approach will be limited by the extent of
disease in the renal pelvis, the access that these agents may have to the area
of disease, the sensitivity of the cancer being treated, and the adequacy and
accuracy of initial tumor staging and continued monitoring.

Laser vaporization/coagulation. Transurethral and percutaneous access to
the upper tract have permitted the use of laser therapy in the control of
superficial upper tract transitional cell cancers. This approach is dependent
on accurate staging and adequate visualization of the lesions that need to be
coagulated. Results of this approach are at present too preliminary to assess.
Therapeutic efficacy, however, will depend on staging accuracy on initial
treatment and ease of monitoring such patients for disease recurrence and
possible progression.

General information about clinical trials is also available from the NCI Web site.

Regional Transitional Cell Cancer of the Renal Pelvis and Ureter

Treatment of extensive regional disease has thus far not had well-documented
success by either radiation or systemic chemotherapy. Patients with extensive
regional disease should be considered for clinical trials.

General information about clinical trials is also available from the NCI Web site.

Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter

The prognosis for any patient with metastatic or recurrent transitional cell
cancer is poor. The proper management of recurrence depends on the sites of
recurrence, extent of prior therapy, and individual patient considerations.
Chemotherapy regimens that have been shown effective for metastatic bladder
cancer have generally been applied to transitional cell cancers arising from
other sites. Patients with distant metastases have a poor prognosis and can
be appropriately offered treatment on a clinical trial.

In patients with metastatic or recurrent transitional cell carcinoma of the
bladder, combination chemotherapy has produced high response rates and
occasional complete responses.[1,2] Results from a randomized trial that
compared methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) to
single-agent cisplatin in advanced bladder cancer show a significant advantage
with M-VAC in both response rate and median survival. The overall response
rate with M-VAC in this cooperative group trial was 39%.[3]

Other chemotherapy agents that have shown activity in metastatic transitional
cell cancer include the following:[4-8][Level of evidence: 3iiiDiv]

Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter

The prognosis for any patient with metastatic or recurrent transitional cell
cancer is poor. The proper management of recurrence depends on the sites of
recurrence, extent of prior therapy, and individual patient considerations.
Chemotherapy regimens that have been shown effective for metastatic bladder
cancer have generally been applied to transitional cell cancers arising from
other sites. Patients with distant metastases have a poor prognosis, and can
be appropriately offered treatment on a clinical trial.

In patients with metastatic or recurrent transitional cell carcinoma of the
bladder, combination chemotherapy has produced high response rates and
occasional complete responses.[1,2] Results from a randomized trial that
compared methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) to
single-agent cisplatin in advanced bladder cancer show a significant advantage
with M-VAC in both response rate and median survival. The overall response
rate with M-VAC in this cooperative group trial was 39%.[3]

Other chemotherapy agents that have shown activity in metastatic transitional
cell cancer include the following:[4-8][Level of evidence: 3iiiDiv]

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of transitional cell cancer of the renal pelvis and ureter. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment are:

Timothy Gilligan, MD (Cleveland Clinic Taussig Cancer Institute)

Andrew Stephenson, MD (Cleveland Clinic)

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